Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: a possible role in blood-brain barrier dysfunction.
Yvan Gasche,Miki Fujimura,Yuiko Morita-Fujimura,Jean-Christophe Copin,Makoto Kawase,Justin Massengale,Pak H. Chan +6 more
TLDR
The appearance of activated MMP-9 after 4 hours of ischemia in correlation with BBB permeability alterations suggests that M MP-9 may play an active role in early vasogenic edema development after stroke.Abstract:
During cerebral ischemia blood-brain barrier (BBB) disruption is a critical event leading to vasogenic edema and secondary brain injury. Gelatinases A and B are matrix metalloproteinases (MMP) able to open the BBB. The current study analyzes by zymography the early gelatinases expression and activation during permanent ischemia in mice (n = 15). ProMMP-9 expression was significantly (P < 0.001) increased in ischemic regions compared with corresponding contralateral regions after 2 hours of ischemia (mean 694.7 arbitrary units [AU], SD ± 238.4 versus mean 107.6 AU, SD ± 15.6) and remained elevated until 24 hours (mean 745.7 AU, SD ± 157.4). Moreover, activated MMP-9 was observed 4 hours after the initiation of ischemia. At the same time as the appearance of activated MMP-9, we detected by the Evan's blue extravasation method a clear increase of BBB permeability. Tissue inhibitor of metalloproteinase-1 was not modified during permanent ischemia at any time. The ProMMP-2 was significantly (P < 0.05) increased only after 24 hours of permanent ischemia (mean 213.2 AU, SD ± 60.6 versus mean 94.6 AU, SD ± 13.3), and no activated form was observed. The appearance of activated MMP-9 after 4 hours of ischemia in correlation with BBB permeability alterations suggests that MMP-9 may play an active role in early vasogenic edema development after stroke.read more
Citations
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Mechanisms, challenges and opportunities in stroke
TL;DR: This new research focus addresses an important need in stroke research, provides challenges and opportunities that can be used to therapeutic advantage and is focused on how blood vessels and brain cells communicate with each other.
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Reactive oxygen radicals in signaling and damage in the ischemic brain.
TL;DR: Transgenic or knockout mice with cell- or site-specific prooxidant and antioxidant enzymes provide useful tools in dissecting the events involving oxidative stress in signaling and damage in ischemic brain injury.
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Effects of Matrix Metalloproteinase-9 Gene Knock-Out on the Proteolysis of Blood–Brain Barrier and White Matter Components after Cerebral Ischemia
Minoru Asahi,Xiaoying Wang,Tatsuro Mori,Toshihisa Sumii,Jae-Chang Jung,Michael A. Moskowitz,M. Elizabeth Fini,Eng H. Lo +7 more
TL;DR: Data demonstrate that the protective effects of MMP-9 gene knock-out after transient focal ischemia may be mediated by reduced proteolytic degradation of critical blood–brain barrier and white matter components.
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Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat
TL;DR: The results provide direct evidence that MMPs open the BBB by degrading TJPs and that an MMP inhibitor prevents degradation of the TJPs by M MPs.
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S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death.
Zezong Gu,Marcus Kaul,Boxu Yan,Steven J. Kridel,Jiankun Cui,Alex Y. Strongin,Jeffrey W. Smith,Robert C. Liddington,Stuart A. Lipton +8 more
TL;DR: Findings suggest a potential extracellular proteolysis pathway to neuronal cell death in which S-nitrosylation activates MMPs, and further oxidation results in a stable posttranslational modification with pathological activity.
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